Pembrolizumab is a full-length human immunoglobulin G4 (IgG4) monoclonal antibody directed against the immune checkpoint PD-1 to remove its binding with PD-L1 and thus to restore an anti-tumor immune response of T cells. Pembrolizumab is one of the most advanced immune checkpoint inhibitors for cancer care. Apart from rare and serious adverse effects, its favorable tolerance profile enables to treat fragile patients who have often no other choice than best supportive care. The effective retained dose of pembrolizumab is a venous administration of 200 mg every 3 weeks until disease progression, intolerance or up to 24 months. Pembrolizumab has already proven its efficacy and thus obtained marketing authorization in so-called hot or hypermutated tumors or tumors expressing PD-L1 such as melanomas, non-small cell lung cancers, urothelial carcinomas, cervical cancer, etc. Pembrolizumab is also authorized in the United States in the treatment of mismatch repair-deficient tumors or with microsatellite instability. The current challenge is to expand its use in tumor types that are supposed to be less immunogenic, for example, by attempting to warm up the tumor microenvironment, or by combining pembrolizumab with other molecules. An acceptable toxicity profile of such combinations remains to explore. We review here the current indications of this drug, the main prognostic and predictive factors of its efficacy as well as the potential forthcoming indications.

IMPORTANCE ERBB2-low (ie, ERBB2 immunohistochemistry score of 1+ or 2+ in the absence of ERBB2 gene amplification) breast cancer (BC) is a new entity, with emerging dedicated treatments. Little is known about its prognosis and response to conventional therapy compared with ERBB2-zero breast tumors (ie, those with an immunohistochemistry score of 0). OBJECTIVE To compare the outcomes for patients with ERBB2-low metastatic BC (MBC) with those of patients with ERBB2-zero MBC. DESIGN, SETTING, AND PARTICIPANTS This cohort study was conducted from the Epidemiological Strategy and Medical Economics MBC platform and included patients with MBC

Background: Trastuzumab emtansine (T-DM1) has shown great effectiveness in treating HER2-positive metastatic breast cancer, but therapies after T-DM1 progression are still controversial. Here, we report the real-world data of tyrosine kinase inhibitors (TKIs) based therapy in T-DM1 resistant HER2-positive metastatic breast cancer.Methods: From August 2019 to April 2021, 48 HER2-positive metastatic breast cancer patients received TKIs-based therapy after T-DM1 progression in Jiangsu Province Hospital. We evaluated the efficacy and safety of TKIs in treating T-DM1 resistant HER2-positive metastatic breast cancer.Results: 48 patients received TKIs-based therapies as a second or later line therapy. 46 (95.8%) patients received a combined therapy, including TKIs plus capecitabine, vinorelbine or trastuzumab. 2 (4.2%) patients received TKIs alone. The median progression-free survival (PFS) was 10.5 months (95%CI 5.432-15.568). Objective response rate (ORR) was 17.4%, and clinical benefit rate (CBR) was 73.9%. For patients who had brain metastasis (n¼11), the median PFS was 10.5 months ) and intracranial ORR was 27.3%. No difference was observed between lapatinib (n¼32) and pyrotinib (n¼16) groups (8.0 months vs. 13.3 months, P¼0.243). The most common adverse events were hand-foot syndrome (11, 22.9%) and thrombocytopenia (10, 20.8%).Conclusions: TKIs-based therapy could improve the survival of T-DM1 resistant HER2positive metastatic breast cancer patients, including those with brain metastasis. This provides a new therapeutic option for HER2-positive breast cancer treatments.Legal entity responsible for the study: The authors.